The present invention relates to a process for the preparation of macrocyclic ester compounds from oligoesters by thermal cleavage in the presence of thermostable benzene derivatives. For the purposes of the present invention, thermostable refers to compounds which behave mostly inert during the oligoester cleavage at temperatures between 200xc2x0 C. and 350xc2x0 C.
Musk fragrances are present in many perfume oils in not inconsiderable amounts. Accordingly, the annual worldwide requirement for musk fragrances is several thousand tons. By far the largest part is provided by the so-called polycyclic aromatic musk fragrances. It has become known that polycyclic aromatic musk fragrances can only be biodegraded with difficulty and consequently, being extremely lipophilic compounds, exhibit bioaccumulative behavior, i.e. they are able to accumulate in the fatty tissue of organisms. In the perfume industry, there is therefore, a pressing need for biodegradeable musk fragrances which are suitable both in terms of the odiferous properties and also in terms of price as replacements for the polycyclic aromatic compounds. In contrast to the polycyclic aromatic compounds, macrocyclic musk fragrances are regarded as biodegradeable (U.S. Pat. No. 6,034,052). The known processes cannot be carried out economically in a satisfactory manner.
It is known that macrocyclic ester compounds can be prepared by depolymerization of linear oligoesters of the corresponding aliphatic hydroxycarboxylic acids or dicarboxylic acids and alkylene glycols. The thermal depolymerization is usually carried out without a diluent under vacuum ( less than 100 hPa) and at high temperatures (200-300xc2x0 C.) in the presence of a catalyst. A codecisive factor for the cleavage yield achieved here is the molecular weight of the oligoester used. For this reason, control of this parameter during the oligoester formation is important. The condensation reaction must, accordingly, be terminated at almost complete conversions before the onset of the molar mass build-up typical of the polyester reaction. A measure which can be used here is, for example, the monitoring of the product viscosity. Alternatively, the condensation and thus, the oligoester formation can be carried out in the solvent chosen for the cleavage in order to avoid high molecular weights. EP A 0 260 680 has already indicated that it may be advantageous to control the molecular weight and the viscosity of the oligoesters used by targeted termination with monocarboxylic acids and/or monofunctional alcohols. Polyesters with acid and OH numbers below 20 or below 10, respectively, may be particularly advantageous.
During the depolymerization, the desired cyclization reaction is accompanied by a further polycondensation of the linear polyester and a further intermolecular crosslinking reaction. The yield of product decreases significantly as a result. Moreover, the crosslinking reactions lead to an increase in the viscosity and to adhesion of the product to the wall of the reactor. This favors the onset of decomposition reactions of the product; the decomposition products may considerably impair the odiferous properties.
These disadvantages in the case of depolymerization without a diluent can be overcome by carrying out the reaction in an inert reaction medium with a high boiling point. The choice of reaction medium here is decisive for the reaction yield which can be achieved and the quality of the product and thus also for the economic efficiency of the process. For example, EP A 0 260 680 has proposed olefin polymers, JP A 55-120 581 has proposed polyesters, polyether glycols, polyether glycol esters or only polyglycols, DE A 3225431 has proposed paraffins, and EP A 0 739 889 has proposed polyethylene glycol dialkyl ethers as high-boiling medium.
Although the use of these auxiliaries can increase the product yield relative to a cleavage without a diluent, said auxiliaries have the disadvantage that they mostly have a high melting point, which makes handling difficult. This disadvantage is all the more serious since one important requirement in the art is that the thermostable reaction medium which is left behind in the distillation still can be removed from the reactor easily when the reaction is interrupted or complete, which is virtually impossible in the case of the known processes with the traditional reaction media.
In the case of the polyether glycols used and in the case of the polyether glycol esters (JP-A 55-120 581), there is another significant disadvantage in that they have functional groups which participate in the polymerization in an undesired manner, possibly leading to significant yield losses. In addition, in the case of the paraffins, the difficulty also arises that they have relatively high vapor pressures compared with the reactants and therefore also convert to the vapor phase. For this reason, in the case of these paraffins, isolation of the product, which follows the depolymerization of the oligoester, is associated with significantly higher expenditure.
Moreover, high-boiling reaction media such as, for example paraffins (DE-A 32 25 341) or olefin polymers (EP-A 0 260 680) are less suitable solvents for all linear poly- or oligoesters. In many cases they only disperse said esters, and the particles may coagulate to form blocks. A remedy is achieved in most cases by further dilution, as a result of which the space-time yield is significantly reduced, as is the case with known processes.
In addition, JP-B 55-120581 describes a process for carrying out the depolymerization and cyclization in the presence of polyoxyalkylene glycol and derivatives thereof, monohydric alcohols and derivatives thereof or monobasic fatty acids and derivatives thereof which in each case have a high boiling point. According to this process, ether bonds in the polyoxyalkylene glycol added are broken and, as a result, various degradation products or gases are formed and, consequently, the vacuum is lower or the quality of the resulting macrocyclic ester compound is impaired. In addition, the odor of the monohydric alcohol or of the monobasic acid or of derivatives thereof mix with the distillate and as a result the scent of the macrocyclic ester compound is impaired and its use as a perfume is impeded. These phenomena are regarded as disadvantages of these customary processes.
Finally, the use of polyethylene glycol dialkyl ethers (EP A 0 739 889) is associated with the disadvantage that the desired effect of an increase in the yield is achieved only at sufficiently great dilution ratios; for example, in EP A 0 739 889, dilution ratios between 5 and 1000 parts by weight of polyethylene glycol dialkyl ether to 1 part by weight of oligomer are given. A further important disadvantage of the use of polyethylene glycol dialkyl ethers is also that a work-up of the solvent is not readily possible and therefore, by-products which contaminate the solvent considerably limit the suitability of the solvent.
The object of the present invention was, therefore, to find a preparation process for macrocyclic ester compounds with which as high a reaction yield as possible can be achieved and with which, the solvent costs can also be reduced, by using a solvent which restricts the formation of by-products which prevent use of the macrocyclic ester compounds as a fragrance, which has a low melting point and thus, good handling properties, which simplifies product separation by virtue of having a high boiling point, and which can be worked-up readily for reuse in the process without relatively large losses as a result of residue formation.
We have now found a process for the preparation of macrocyclic ester compounds obtainable from linear oligoesters by thermal depolymerization with or without the addition of catalysts, which is characterized in that the depolymerization is carried out in thermostable benzene derivatives at a pressure of less than 100 hPa, and at temperatures of from 200xc2x0 C. to 350xc2x0 C., 0.1 to 1000 parts by weight of solvent being used per part by weight of the oligoester.
Macrocyclic ester compounds which can be prepared by the process according to the present invention are generally 14- to 17-member ring systems. They can be described by the following general formula 
in which
x and y produce in total a number of at least 10 and at most 13;
A may be a methylene group or a heteroatom, such as oxygen or sulfur;
B may be a methylene group or a carbonyl group or
A and B taken together may be a carbon double-bond.
Preferably, the process according to the present invention may be used to prepare macrocyclic lactones of xcfx89-hydroxycarboxylic acids which may optionally comprise a double bond and/or a further heteroatom, e.g. oxygen, or macrocyclic lactones of dicarboxylic acids and diols.
Particularly preferably, the process according to the present invention can be used to prepare 1,15-pentadecanolide, cis-/trans-1,15-pentadec-11-enolide, cis-/trans-1,15-pentadec-12-enolide or mixtures thereof, 1,16-hexadecanolide or trans-1,16-hexadec-9-enolide or ethylene tridecadioate, ethylene dodecadioate or ethylene undecadioate or mixtures thereof.
The linear oligoesters for the process according to the present invention can be described by the following general formula: 
in which
x and y produce in total a number of at least 10 and at most 13;
A may be a methylene group or a heteroatom, such as oxygen or sulfur;
B may be a methylene group or a carbonyl group or
A and B taken together may be a carbon double-bond.
For the process according to the present invention, oligoesters of aliphatic hydroxycarboxylic acids or oligoesters of dicarboxylic acids with diols are preferred.
Linear oligoesters as starting compounds for the process according to the present invention can be prepared by condensation of difunctional compounds of the formula 
in which
x and y produce in total a number of at least 10 and at most 13;
A may be a methylene group or a heteroatom, such as oxygen or sulfur;
B may be a methylene group or A and B taken together may be a carbon double-bond;
R1 may be a hydrogen atom or a lower alkyl group, such as, for example, methyl or ethyl,
or of the formula 
in which
x and y produce in total a number of at least 10 and at most 13;
R1 may be a hydrogen atom or a lower alkyl group, such as, for example, methyl or ethyl,
in a manner known per se (DE B 2731543; Houben-Weyl, Methoden der Organischen Chemie [Methods of Organic Chemistry] Vol. 4/2, p. 787ff. and Vol. 6/2, p. 738f.).
The process according to the present invention is based on a thermal cleavage of oligoesters to the desired macrocyclic esters. The cleavage reaction is carried out in a vacuum and at very high temperatures in an inert, high-boiling reaction medium with or without the addition of catalysts, a rectification column being placed on top of the container in which the chemical reaction takes place and used to separate off and concentrate the macrocyclic esters formed. Here, the thermal cleavage is carried out in thermostable, high-boiling alkylbenzene or benzene derivatives, e.g. of the formula 
in which
R1 is 
xe2x80x83and
R2 is H or CH3 
as reaction medium. By using these thermostable benzene derivatives, the yield is significantly increased compared with a cleavage without a diluent. The derivatives of type a) are essentially isomeric dibenzyltoluenes, b) refers to the group of diarylalkyls, c) represents the bi- or triaryl oxides, d) includes the group of terphenyls and their partially hydrogenated analogues and, finally, e) represents the alkylated or non-alkyl-substituted benzyltoluenes.
Preferred thermostable benzene derivatives are dibenzyltoluenes and isomer mixtures thereof, and terphenyls and their partially hydrogenated analogues. A more preferred embodiment is dibenzyltoluenes and isomeric mixtures thereof.
The thermostable benzene derivatives for the process according to the present invention have a low melting point and a high boiling point at the same time. However, despite the high boiling point, they are very vaporizable and can, therefore, be separated readily from high-boiling impurities. Their use as reaction medium is therefore advantageous both with regard to handling and also with regard to product separation. For example separation of the product from the reaction medium is possible in a rectification column with only a few separation stages, the number of separation stages required and the reflux ratio to be set being governed by the difference in boiling points between the macrocyclic ester formed and the solvent used.
If benzene derivatives are used, reaction yields of more than 90% can be achieved. In this connection, it is essential for the economic efficiency of the process that the high reaction yields can be achieved at low solvent costs. This is possible, in particular, by setting low dilution ratios of solvent to oligomer during the depolymerization and, moreover, working-up the spent solvent for recycle and reuse in the process.
It was surprising that the benzene derivatives used as reaction medium for the thermal depolymerization are stable. This was unexpected since alkyl- and benzyl-substituted benzene derivatives in the presence of the catalysts suitable for the depolymerization and at the high reaction temperatures are able to undergo transalkylation reactions, in the course of which high-boiling and low-boiling components are formed as a result of disproportionation. As well as a solvent loss, this would also permanently impair the suitability of the solvent since low-boiling solvent constituents accumulate in the product, and the high-boiling constituents can lead to resinification of the distillation bottoms.
In particular, dibenzene toluene, which is available in technical-grade form as an isomer mixture, has an excellent profile of properties for the process according to the present invention, since it permits particularly effective separation from the product which distills off, as a result of its high, comparatively narrow boiling range.
For reasons of simplicity, the condensation of the difunctional compounds to give the linear oligoesters is connected upstream of the process according to the present invention.
Implementation of the process is, therefore, first started with the condensation, which can be carried out in accordance with known methods at elevated temperatures with or without catalyst. In this process, hydroxycarboxylic acids, or hydroxycarboxylic esters are heated, or the dicarboxylic acids or esters thereof are reacted with a glycol. The water which forms in the process or the alcohol is distilled off or removed using an entrainer or with the help of a slight vacuum. The removal of some or all of the excess glycol can also be carried out in the subsequent process step, i.e. from the cleavage reactor.
The oligomer is then transferred to the cleavage reactor, into which the high-boiling medium has been introduced together with the catalyst component. The catalysts used are customary catalysts known per se (EP A 0 739 889), such as, for example, alkali metals and alkaline earth metals and salts thereof, and salts and organometallic compounds of the elements manganese, cadmium, iron, cobalt, tin, lead, aluminium, zirconium and titanium. The amount of catalyst is in the range from 0.1 to 20% by weight, preferably in the range from 0.5 to 10% by weight, based on 100% by weight of oligoester, depending on the corresponding type used.
At high temperatures between 200xc2x0 C. and 350xc2x0C., preferably between 220xc2x0 C. and 290xc2x0 C., and at a vacuum of less than 100 hPa, the depolymerization then takes place. The cleavage products preferably rise during the process in the form of vapors and are thus, withdrawn directly from the reaction in the liquid phase. The product components can be separated from the components of the reaction medium in a rectification column placed on top of the reaction container, at the upper end of the column the product components being withdrawn, and at the lower end of the column the components of the reaction mixture being taken off for recycling to the reaction container. The column is operated for this purpose at pressures of  less than 100 hPa, the pressure range preferably being from 5 to 95 hPa, particularly preferably from 10 to 80 hPa. At the top of the column, a reflux ratio between 0.1 and 100, preferably between 10 and 80, is to be set.
The process can either be carried out either batchwise or continuously. In the case of a batchwise procedure, the oligomer is introduced in one portion together with the solvent and cleaved in one batch. By contrast, in the case of the continuous procedure, the oligomer is metered into the reaction medium during the cleavage in portions or with a constant material stream. Preference is given to carrying out the continuous procedure since in this case the product can be removed from the top of the column with a constant composition.
The solvent is recovered by partial evaporation, for example in a thin-layer evaporator at pressures of less than 100 hPa, preferably at pressures of less than 50 hPa.
A very wide variety of macrocyclic ester compounds can be prepared by this process. It is particularly suitable for the preparation of macrocyclic esters having 6 to 20, preferably 13 to 16, carbon atoms, since they can be prepared in particularly pure form by the process according to the present invention, which is highly beneficial to their use as fragrances. In particular, using the process according to the present invention, it is also possible to prepare the mixtures of ethylene dodecanedioate and ethylene undecanedioate described in U.S. Pat. No. 6,034,052.